The general long-term goal of this project is to identify the effects of brain injury on endogenous neural stem cells (NSCs). Specifically this proposal aims to identify the acute response of these NSCs to a perinatal hypoxic/ischemic (H/I) brain insult. Once defined, this response could provide a potential therapeutic target for preventing consequence of perinatal H/I such as cerebral palsy, mental retardation, and a spectrum of other neurological disorders. NSCs are known to reside as a quiescent population of cells in the subventricular zone (SVZ) throughout life. These cells can be induced to proliferate both in vitro and in vivo with specific growth factors. We have observed that NSCs are more abundant in dissociated cultures of the SVZ after H/I; therefore, the immediate goal is to define the acute effects of perinatal H/I on SVZ NSCs. My central hypothesis is that perinatal H/I recruits NSCs to a more proliferative state, thereby expanding the total population. I will determine the effect of H/I on levels of growth factors and their receptors in the SVZ as well as the dose-response of NSCs to these growth factors after H/I. I will also determine the effects of H/I on the proliferation kinetics and mode of division of NSCs. These experiments can potentially identify a novel target for therapeutic strategies in perinatal brain injury.